Alzheimer's disease (AD) is an age-related illness that occurs in almost 50% of peopls over 80 years old. The hallmarks of AD include specific abnormalities in brain structures. Particularly, biomedical magnetic resonance imaging (MRI) has demonstrated a significant loss of gray matter in AD patients. However, the exact mechanism of this cerebral atrophy in AD remains unknown. This project will address this problem. Our goal of understanding the structural changes in AD will be addressed by combining expertise in three research areas; state-of-the-art microscopic MRI, tissue segmentation, and mouse genetic engineering. The integration of these techniques for animal modeling of Alzheimer's disease will promote the understanding of the neuronal progression in this disease and lead to early diagnosis. Based on the evidence that presence of the E4 allele of apolipoprotein E. (APOE)) significantly correlates with the risk of an individual developing AD, we hypothesize that MRI will show cerebral atrophy in brains of transgenic mice carrying the human APOE4 allele. It is expected that this will occur at a stage before behavioral analysis of cognitive capabilities shows abnormalities. Four groups of mice will be imaged using MRI. Three groups are the transgenic mouse lines carrying and expressing human APOE, 2, 3, and 4 genes, respectively, and one group is composed of nontransgenic age-matched controls. Each group will have twenty mice. The imaging experiment will be repeated at one-month intervals throughout the aging process. All MR images of mice brains will be segmented into gray matter (GM) and white matter (WM) images by a fuzzy classifier method. The mean and standard error of the GM and WM will be calculated for each group. An ANOVA statistical analysis will be performed on the images at each age to determine the GM and WM volume difference and to assess the statistical significance for these four groups. The relationship between changes in structure and age will be determined. The results from this transgenic animal model study will provide a means to characterize the development of Alzheimer's disease (neuronal destruction and cognitive decline) which may result from the APOE allele interactions.